The sympathetic nervous system contributes to certain types of chronic pain states such as complex regional pain syndrome (CRPS). Many studies have evaluated sympathetic modulation of nociceptors utilizing animal models of hyperalgesia that typically involve a peripheral nerve injury. These studies have demonstrated that NPY, a sympathetically derived neuropeptide, provides an important although highly complex neuromodulatory function after peripheral nerve injury. However, few studies have evaluated NPY modulation of nociceptors under control or "in-injured" conditions, which is the broad objective of this research proposal. We believe that understanding how NPY functions under basal conditions is critical to understanding how it functions in response to injury. The specific aims are: 1) to characterize the pharmacological effects of NPY receptor agonists for modulating the initiation of neurogenic inflammation; 2) to determine whether NPY receptor agonists inhibit capsaicin-evoked hyperalgesia following administration to the rat dental pulp; 3) to evaluate the molecular basis for NPY pharmacology by identifying specific NPY receptor subtypes expressed on the capsaicin-sensitive class of trigeminal sensory neurons and 4) to evaluate the effects of nerve injury on specific aims #1-3. Collectively, these parametric, integrated and multidisciplinary research plan will seen to both address an important scientific question, and to provide an excellent opportunity for comprehensive scientific training.